Back to discover

Protein / target

Tyrosine-protein kinase JAK3

Encoded byJAK3P52333Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
11
Approved medicines
Open Targets target-level
10
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Non-membrane spanning protein tyrosine kinase

Strongest disease association

Severe Combined Immunodeficiency

Via encoding gene JAK3 · Genetic evidence · score 0.87

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation.

View complete UniProt function annotation

Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A and STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion

Subcellular location

Endomembrane systemCytoplasm
Domains and Gene Ontology detail (46)

Domains & features

FERMSH2; atypicalProtein kinase 1Protein kinase 2

Gene Ontology

  • Ccytoplasmic side of plasma membrane
  • Ccytosol
  • Cendosome
  • Cextrinsic component of cytoplasmic side of plasma membrane
  • Cextrinsic component of plasma membrane
  • Cplasma membrane
  • FATP binding
  • Fgrowth hormone receptor binding
  • Fnon-membrane spanning protein tyrosine kinase activity
  • Fprotein phosphatase binding
  • Fprotein tyrosine kinase activity
  • Padaptive immune response

1124 aa · 125 kDa · 3 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Receptor tyrosine kinase signallingUniProtImmune signallingUniProt · GOApoptosis & cell deathGO
View supporting evidence

Receptor tyrosine kinase signalling

  • ·Non-receptor tyrosine kinase involved in various processes such as cell growth, developm…

Immune signalling

  • ·Non-receptor tyrosine kinase involved in various processes such as cell growth, developm…
  • ·adaptive immune response
  • ·B cell differentiation
  • ·cytokine-mediated signaling pathway

Apoptosis & cell death

  • ·negative regulation of thymocyte apoptotic process
  • ·regulation of apoptotic process
  • ·regulation of T cell apoptotic process

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Drugs targeting this protein

1

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

delgocitinib
ApprovedInhibitor

Janus Kinase (JAK) inhibitor

Acts on a complex — shared with JAK1, JAK2, TYK2 · 1 of 4 recorded protein targets

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene JAK3

Gene-level evidence surfaced through the gene JAK3that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Severe Combined Immunodeficiency
0.88Well supported

Genetic evidence dominant · Open Targets 0.54

Colitis, Ulcerative
0.81Well supported

Clinical evidence dominant · Open Targets 0.65

Myelofibrosis
0.79Well supported

Clinical evidence dominant · Open Targets 0.61

Arthritis, Rheumatoid
0.76Well supported

Clinical evidence dominant · Open Targets 0.62

Dermatitis, Atopic
0.71Moderately supported

Clinical evidence dominant · Open Targets 0.58

View evidence synthesis (5)
Severe Combined ImmunodeficiencyWell supported
0.88
agreement 0.741.00
Genetic94%Literature6%

Open Targets aggregate 0.54 · 2 independent evidence families

Colitis, UlcerativeWell supported
0.81
agreement 0.690.92
Clinical68%Somatic mutation28%RNA expression2%Literature2%

Open Targets aggregate 0.65 · 4 independent evidence families

MyelofibrosisWell supported
0.79
agreement 0.690.90
Clinical66%Somatic mutation19%Animal model15%Literature1%

Open Targets aggregate 0.61 · 4 independent evidence families

Arthritis, RheumatoidWell supported
0.76
agreement 0.610.92
Clinical90%Literature10%

Open Targets aggregate 0.62 · 2 independent evidence families

Dermatitis, AtopicModerately supported
0.71
agreement 0.580.85
Clinical98%Literature2%RNA expression1%

Open Targets aggregate 0.58 · 3 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Colitis, Ulcerative0.65
Arthritis, Rheumatoid0.62
Myelofibrosis0.61
Dermatitis, Atopic0.58
Alopecia Areata0.57
Arthritis, Psoriatic0.56
Crohn's Disease0.56
Acquired polycythemia vera0.55
Severe Combined Immunodeficiency0.54

Drug development

20 compounds recorded · 11 approved · 9 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph: these count different sets and are not a subset relation.

View all recorded compounds (10)
TOFACITINIBApproval
PEFICITINIBPhase 3
RITLECITINIB TOSYLATEApproval
FILGOTINIB MALEATEApproval
UPADACITINIBApproval
RUXOLITINIBApproval
RITLECITINIBApproval
DELGOCITINIBApproval
R-333Phase 2
UPADACITINIB HEMIHYDRATEApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (go cc high conf and uniprot loc med conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (literature and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (12)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · GO CC high confAB · UniProt loc med confAB · Human Protein Atlas locPR · LiteraturePR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

10

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (6)

ClinicalTrials.gov via the drug-target graph.

What's happening now

4

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Label change2026-06-30

    Label change: DELGOCITINIB (NDA219155)

    fda · regulatory · fda · via delgocitinib

  2. Regulatory approval2025-07-23

    Approval: DELGOCITINIB (NDA219155)

    fda · regulatory · fda · via delgocitinib

  3. New publication2025-04-16
    Efficacy and safety of topical delgocitinib cream versus oral alitretinoin capsules in adults with severe chronic hand eczema (DELTA FORCE): a 24-week, randomised, head-to-head, phase 3 trial.

    Lancet (London, England) · 2025 · 12 citations · Europe PMC · via delgocitinib

  4. Regulatory approval2024-09-19

    Approval: Anzupgo (EMA)

    ema · regulatory · ema · via delgocitinib

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.